Noradrenergic Modulation of Effective Connectivity in Autism Spectrum Disorder

Background: Previous experiments have demonstrated decreased functional connectivity in subjects diagnosed with ASD when compared to controls, during language tasks. Therefore, drugs that affect functional connectivity may be beneficial in ASD. Stress causes a decrease in the Semantic Network Flexibility (SNF), and the noradrenergic system is upregulated in stress. In addition, the SNF impairment is reversed by administration of centrally mediated noradrenergic antagonists. Propranolol (β-blocker) has also shown benefit in language and social behavior in ASD.

Objectives: We proposed to find whether administration of propranolol in ASD increases functional connectivity observed during language tasks.

Methods: Subjects with ASD and age and IQ-matched controls without neurodevepmental diagnoses were scanned using a Philips 3T Signa scanner, and a 8-channel head coil with the following parameters: TR = 3s; Flip Angle = 90; 3.75x3.75 in-plane resolution; 64x64 matrix reconstructed to 128x128; 35 axial slices; 5mm slice thickness. Subjects were instructed to respond to the meaning (semantic) or the pronunciation (phonological) of a word related to a cue word in two block-design tasks. Data was preprocessed and analyzed using SPM5.

Results: Preliminary results replicate reports that individuals with ASD have a lesser functional connectivity when compared to controls. In addition, administration of propranolol has revealed a significant increase in the functional connectivity between selected brain regions.

Conclusions: These results reveal an increased functional connectivity upon administration of propranolol in ASD. This may suggests an anatomical substrate of the effects of noradrenergic agents during tasks involving a network search within the brain.